Hyaluronic acid-poly (vinyl alcohol) composite hydrogels with self-assembled peptide nanofibers as Bruch's membrane mimics for age-related macular degeneration treatment.
Peptide nanofibers are powering a new approach to retinal regeneration. Researchers in India just took a big swing at age-related macular degeneration (AMD), one of the toughest eye problems out there. Their team engineered an injectable hydrogel that combines hyaluronic acid and polyvinyl alcohol, then reinforced the whole thing with self-assembling peptide nanofibers.
Int J Biol Macromol
by Bagewadi S, Parameswaran S, Sethuraman S et al.
“Hyaluronic acid-poly (vinyl alcohol) composite hydrogels with self-assembled peptide nanofibers as Bruch's membrane mimics for age-related macular degeneration treatment. Bagewadi S(1), Parameswaran S(2), Sethuraman S(1), Subramanian A(3). Author information: (1)Tissue Engineering & Additive Manufacturing (TEAM) Lab, Centre for Nanotechnology & Advanced Biomaterials, ABCDE Innovation Centre, School of Chemical & Biotechnology, SASTRA Deemed University, Thanjavur, 613401, India. (2)Radheshyam Kanoi Stem Cell Laboratory, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Vision Research Foundation, Chennai, India. (3)Tissue Engineering & Additive Manufacturing (TEAM) Lab, Centre for Nanotechnology & Advanced Biomaterials, ABCDE Innovation Centre, School of Chemical & Biotechnology, SASTRA Deemed University, Thanjavur, 613401, India. Electronic address: anuradha@bioengg.sastra.edu. Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the elderly, and effective curative therapies are not available. This study presents a tissue-engineering strategy for retinal regeneration using an injectable, in situ-forming hydrogel composed of thiol-functionalized hyaluronic acid (HA-SH) and polyvinyl alcohol (PVA), reinforced with peptide nanofibers. Decellularized Bruch's membrane derived from goat eyes was used as a control and exhibited a fiber diameter of 75.09 ± 12.99 nm, thickness of 6.26 ± 1.12 μm, and hydrophilic properties (contact angle: 39.46° ± 0.46). In comparison, the GAGA-YIGSR-based hydrogel membrane demonstrated comparable structural features with a fiber diameter of 92.38 ± 16.37 nm, a thickness of 13.43 ± 3.64 μm, and a contact angle of 72.13° ± 2.98. The HA-SH/PVA hydrogel incorporating peptide nanofibers significantly enhanced retinal pigment epithelium (RPE) cell viability, adhesion, proliferation, phagocytosis, and RPE-specific gene expression compared to the peptide-free hydrogel. In vivo functional evaluation using H&E-stained retinal sections revealed that the HA-SH/PVA hydrogel containing the GAGA-YIGSR peptide markedly improved RPE cell organization, ONL nuclei density (1578.22 ± 187.03), ONL cell rows (9.02 ± 1.74), linear RPE cell count (10.6 ± 2.6), and ONL thickness (35.52 ± 4.44 μm) relative to saline controls. Furthermore, the hydrogel preserved retinal barrier integrity and ultrastructural parameters, including tight-junctions, subretinal pigment epithelium space (7.26 ± 4.92 μm), BM thickness (5.91 ± 1.07 μm), collagen area (21.74 ± 3.48%), collagen thickness (81.8 ± 24.17 μm), and collagen pore area (17.72 ± 9.19%), which were comparable to those of healthy controls. In conclusion, this study successfully developed and evaluated an injectable peptide-functionalized hydrogel as a promising therapeutic scaffold for retinal tissue regeneration in AMD. Copyright © 2026. Published by Elsevier B.V. Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.”
Why bother with this combo? The goal: mimic Bruch’s membrane, the thin tissue layer critical for retinal health and totally shot in AMD. The researchers measured up their hydrogel against the real thing (decellularized goat Bruch’s membrane). The numbers lined up surprisingly well — fiber diameter, thickness, and even hydrophilicity were all close, and the peptide-enhanced version held its own.
Here’s what matters for peptide fans:
Adding the GAGA-YIGSR peptide nanofibers made a real difference. Retinal pigment epithelium (RPE) cells loved the new hydrogel — better adhesion, more growth, and stronger gene expression.
In animal models, the peptide hydrogel led to better RPE organization and denser, healthier retinal layers compared to controls. The tissue held together more like a healthy retina.
Ultrastructural analysis showed tight junctions, proper collagen structure, and preserved barrier function — all key for long-term eye health.
Translation: this is one of the clearest demonstrations so far that peptide nanofibers can upgrade biomaterial scaffolds for real tissue regeneration, not just in a dish but in living systems. The work adds serious momentum to the idea that peptides should be front-and-center in regenerative medicine toolkits.
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Peptide-based hydrogels are stepping up. This is a field to watch.
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